Wound Healing

Question 1

Give a generalised overview of the process of wound healing.

Answer 1

slide 3
1. injury is caused by trauma
2. cell/matrix damage
3. inflammation
4. -repair - healing and fibrosis/scar
-regenration
- failure of healing

Question 2

What is regeneration?

Answer 2

Replacement of lost or damaged tissue by a similar type derived from the proliferation of the surrounding undamaged cells

Question 3

What is repair?

Answer 3

Replacement of lost or damaged tissue by granulation tissue which later matures into fibrous scar tissue.

Question 4

what is healing?

Answer 4

The process of healing and repair is similar in many tissues

Healing is usually described with reference to a small skin wound.

Question 5

What is healing by primary & secondary intention?

Answer 5

Healing by primary intention: the wound edges are in close apposition (so re-epithelialisation dominates healing)

Healing by secondary intention: the wound is more extensive and the wound edges are widely separated
(granulation tissue covers wound & wound area is reduced by contraction).

You then get re-epithelialisation from wound edges but also from residual appendages (hair follicles etc.)

Question 6

What’s the first thing that happens when you injure yourself (within an hour)?

Answer 6

Haemostasis: involving the connective tissue and epithelium

-Platelet plug formation
-Fibrin clot formation

Question 7

What are some examples of factors which inhibit the formation of the platelet plug and fibrin clot?

Answer 7

Aspirin - pain killer
Warfarin - treat blood clots
factor VIII deficiency (also inhibits wound healing)

Question 8

What follows the process of haemostasis in wound healing (around 48 hours)?

Answer 8

involving the connective tissue and epithelium

Inflammation
Macrophage infiltration
Debridement

Question 9

What happens exclusively in the connective tissue following haemostasis & debridement? (Granulation tissue formation 2 to 5 days)

Answer 9

involving the connective tissue

Granulation tissue formation:
-endothelial cell and fibroblast proliferation
-new blood vessels migrate from the wound edges
-small blood vessels are accompanied by fibroblasts and inflammatory cells
-collagen extra-cellular matrix

Question 10

What is granulation tissue?

Answer 10

A loose cellular connective tissue with many plump, synthetic fibroblasts; dilated irregular blood vessels; and inflammatory cells

Question 11

What happens in the connective tissue after granulation tissue formation (>5 days)?

Answer 11

involving the connective tissue

maturation occurs:

-Decreased cellularity
-Decreased vascularity
-Remodelling of collagen matrix
-Collagen cross linking

INVOLVES MMP’s1 and other proteases

Question 12

What changes in the epithelium are happening alongside all these events in the connective tissue (1 to 3 days)?

Answer 12

Re-epithelialisation:

Proliferation of basal epithelial cells adjacent to the wound

Migration of basal epithelial cells across wound bed under fibrin scab to restore epithelial continuity

Epithelial cells differentiate and stratified squamous structures reform

slide 11 and muska images

Question 13

Summarise the healing of a small skin wound.

Answer 13

1 hour - Haemostasis; platelet plug and clot formation
48 hours - Inflammation and debridement
2-5 days - Granulation tissue formation
>5 days - maturation, remodelling, wound contraction

1-3 days - re-epithelisation
look at slide 10

Question 14

Is the control of wound healing a simple process?

Answer 14

No it’s a complex process involving convergence of signals from many sources.

slide 12

Question 15

What dramatically impaired wound healing in guinea pigs?

Answer 15

Mononuclear (macrophage precursor) depletion

Question 16

What are the traditional functions of macrophages?

Answer 16

-Phagocytosis
-Protease synthesis
-Regulation of immune cell function

Question 17

What is the significance of macrophages in wound healing?

Answer 17

They produce growth factors like:
-FGF a/b, TGF-b, PDGF, VEGF

-other bioactive molecules:
1.Fibroblast recruitment and activity
-cell proliferation
-ECM synthesis
-protease (MMP) synthesis

2. Endothelial cell recruitment and activity

Question 18

What systemic factors could interfere with wound healing?

Answer 18

Age

Nutritional status (e.g vitamin deficiency, protein deficiency)

Iatrogenic (people on steroids)

Pre-existing medical conditions (e.g diabetes)

Question 19

What local factors could affect wound healing?

Answer 19

Blood supply (poor blood supply can lead to infection)
Infection
Persistent irritation
Poor wound stability
Poor apposition of wound edges
Skin wounds: direction of incision- Langers lines
Ionising radiation

Question 20

What are some possible complications of wound healing?

Answer 20

-Wound dehiscence (breakdown of wound)
-Contractures
-Keloid/hypertrophic scar formation
-Weak scars (incisional hernia)
-Pigmentation
-Neoplastic changes (Marjolin’s ulcer)

Question 21

What is a keloid scarring?

Answer 21

A sharply elevated, progressively enlarging scar characterised by the formation of excessive amounts of collagen in the dermis during connective tissue repair.

It may spread beyond the margins of the original wound

Characteristically found in Afro-Carribean populations

Seen on the face but does not affect the oral mucosa

look at slide 16

Question 22

what is a hypertrophic scarring?

Answer 22

Similar to keloid but does not spread beyond the wound margins

Will affect varied population groups

Seen on the face but does not affect the oral mucosa

look at slide 16

Question 23

How do embryonic wounds heal?

Answer 23

Heal without scarring

Question 24

How is scaring on the oral mucosa?

Answer 24

There is still scaring but it is less than the skin